Contents

Metabolism of L-tryptophan into serotonin and melatonin (left) and niacin (right). Transformed functional groups after each chemical reaction are highlighted in red.

Amino acids, including tryptophan, are used as building blocks in protein biosynthesis, and proteins are required to sustain life. Many animals (including humans) cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. Tryptophan is among the less common amino acids found in proteins, but it plays important structural or functional roles whenever it occurs. For instance, tryptophan and tyrosine residues play special roles in "anchoring" membrane proteins within the cell membrane. In addition, tryptophan functions as a biochemical precursor for the following compounds (see also figure to the right):

The disorder fructose malabsorption causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood,[10] and depression.[11]

In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a repressor protein, which binds to the trp operon.[12] Binding of this repressor to the tryptophan operon prevents transcription of downstream DNA that codes for the enzymes involved in the biosynthesis of tryptophan. So high levels of tryptophan prevent tryptophan synthesis through a negative feedback loop, and when the cell's tryptophan levels go down again, transcription from the trp operon resumes. This permits tightly regulated and rapid responses to changes in the cell's internal and external tryptophan levels.

In 2001 a Cochrane review of the effect of 5-HTP and tryptophan on depression was published. The authors included only studies of a high rigor and included both 5-HTP and tryptophan in their review because of the limited data on either. Of 108 studies of 5-HTP and tryptophan on depression published between 1966 and 2000, only two met the authors' quality standards for inclusion, totaling 64 study participants. The substances were more effective than placebo in the two studies included but the authors state that "the evidence was of insufficient quality to be conclusive" and note that "because alternative antidepressants exist which have been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan is limited at present".[27] The use of tryptophan as an adjunctive therapy in addition to standard treatment for mood and anxiety disorders is not supported by the scientific evidence.[28][27][28]

Tryptophan taken as a dietary supplement (such as in tablet form) has the potential to cause serotonin syndrome when combined with antidepressants of the MAOI or SSRI class or other strongly serotonergic drugs.[30] Because tryptophan supplementation has not been thoroughly studied in a clinical setting, its interactions with other drugs are not well known.[27]

Subsequent studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko.[38][43][44][45] It eventually became clear that recent batches of Showa Denko's L-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak.[38][46][47] However, other evidence suggests that tryptophan itself may be a potentially major contributory factor in EMS.[48]

The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001,[38] but continued to limit the importation of tryptophan not intended for an exempted use until 2005.[49]

The fact that the Showa Denko facility used genetically engineered bacteria to produce the contaminated batches of L-tryptophan later found to have caused the outbreak of eosinophilia-myalgia syndrome has been cited as evidence of a need for "close monitoring of the chemical purity of biotechnology-derived products".[50] Those calling for purity monitoring have, in turn, been criticized as anti-GMO activists who overlook possible non-GMO causes of contamination and threaten the development of biotech.[51]

Tryptophan affects brain serotonin synthesis when given orally in a purified form and is used to modify serotonin levels for research.[25] Low brain serotonin level is induced by administration of tryptophan-poor protein in a technique called "acute tryptophan depletion".[61] Studies using this method have evaluated the effect of serotonin on mood and social behavior, finding that serotonin reduces aggression and increases agreeableness.[62]

Tryptophan is an important intrinsic fluorescent probe (amino acid), which can be used to estimate the nature of the microenvironment around the tryptophan residue. Most of the intrinsic fluorescence emissions of a folded protein are due to excitation of tryptophan residues.

^"3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 October 2015. Indole-3-propionate (IPA), a deamination product of tryptophan formed by symbiotic bacteria in the gastrointestinal tract of mammals and birds. 3-Indolepropionic acid has been shown to prevent oxidative stress and death of primary neurons and neuroblastoma cells exposed to the amyloid beta-protein in the form of amyloid fibrils, one of the most prominent neuropathologic features of Alzheimer's disease. 3-Indolepropionic acid also shows a strong level of neuroprotection in two other paradigms of oxidative stress. (PMID10419516 )
Origin: • Endogenous • Microbial

^Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (July 1999). "Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid". J. Biol. Chem. 274 (31): 21937–21942. doi:10.1074/jbc.274.31.21937. PMID10419516. [Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity.

^Fernstrom JD (2012). "Effects and side effects associated with the non-nutritional use of tryptophan by humans". The Journal of Nutrition. 142 (12): 2236S–2244S. doi:10.3945/jn.111.157065. PMID23077193.